Researchers from four organizations have identified more than 200 new proteins that bind to normal and mutant forms of the protein that causes Huntington’s disease (HD).
“We identified a comprehensive set of Htt interactors using two complementary approaches: high-throughput yeast two-hybrid screening and affinity pull down followed by mass spectrometry,” the scientists explain. “This effort led to the identification of 234 high-confidence Htt-associated proteins, 104 of which were found with the yeast method and 130 with the pull downs.”
The investigators then abitrarily picked 60 of the genes to test in fruit flies genetically altered to express features of human HD. “This high-content validation assay showed that 27 of 60 orthologs tested were high-confidence genetic modifiers, as modification was observed with more than one allele,” according to the team.
The new genes and proteins discovered in this study are being screened and analyzed in cultured mammalian cells. The ones that show activity in ongoing experiments will be tested in mouse models of HD.
The research was led by scientists at the Buck Institute and included Fred Hutchinson Cancer Research Center, Prolexys Pharmaceuticals, and Baylor College of Medicine, which performed the testing in fruit flys. The results of the study will be published in the May 11 edition of PLoS Genetics.